Harmful cyanobacterial blooms produce toxins that are a major threat to water quality and human health. Blooms increase with eutrophication and are expected to be amplified by climate change. Yet, we lack a mechanistic understanding on the toxicity of blooms, and their response to the complex interplay of multiple global change factors. Bloom toxicity is determined by a combination of mechanisms acting at different ecological scales, ranging from cyanobacterial biomass accumulation in the ecosystem, to the dominance of toxic species in the community, contribution of toxic genotypes in the population, and the amounts of toxins in cells.